Natural Product: NPC471416

Natural Product IDNPC471416
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Lancerin
IUPAC Name 1,3,7-trihydroxy-4-[(2R,3S,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyxanthen-9-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2436932
PubChem CID 73346479
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0002817] Dibenzopyrans
            • [CHEMONTID:0000200] Xanthenes
              • [CHEMONTID:0000204] Xanthones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey LHOFSAMRRKVGMM-GKYWSENQSA-N
Standard InCHI InChI=1S/C19H18O11/c20-5-11-14(25)15(26)16(27)19(29-11)30-17-9(23)4-8(22)12-13(24)7-3-6(21)1-2-10(7)28-18(12)17/h1-4,11,14-16,19-23,25-27H,5H2/t11-,14-,15+,16-,19+/m0/s1
SMILES OC[C@@H]1O[C@H](Oc2c(O)cc(c3c2oc2ccc(cc2c3=O)O)O)[C@H]([C@@H]([C@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.08 Volume:   381.192
?
Van der Waals volume.
Dense:   1.107 LogP:   0.249
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.012
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.999
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   190.28
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   7.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.263 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.982 Fsp3:   0.316
MCE-18:   88.4
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.621 Fluc inhibitor:   0.281
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.906
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.566
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.257 Promiscuous compounds:   0.796

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.488 MDCK Permeability:   -5.011
Pgp-inhibitor:   0.0 Pgp-substrate:   0.396
PAMPA:   0.996
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.612
20% Bioavailability (F20%):   0.32 30% Bioavailability (F30%):   0.963
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.077 MRP1:   0.138
Plasma Protein Binding (PPB):   84.83% Volume Distribution (VD):   0.01
Fu: 15.586%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.927
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.592
BSEP inhibitor:   0.069

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.034 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.552
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.939
HLM stability:   0.207
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  2.473 Half-life (T1/2):  3.065

ADMET: Toxicity

hERG Blockers:  0.006 hERG Blockers (10um):  0.15
Human Hepatotoxicity (H-HT):  0.548 Drug-induced Liver Injury (DILI):  0.796
AMES Toxicity:  0.776 Rat Oral Acute Toxicity:  0.127
Maximum Recommended Daily Dose:  0.066 Skin Sensitization:  0.976
Carcinogencity:  0.227 Eye Corrosion:  0.0
Eye Irritation:  0.879 Respiratory Toxicity:  0.135
Drug-induced Neurotoxicity:  0.007 Ototoxicity:  0.598
Hematotoxicity:  0.11 Drug-induced Nephrotoxicity:  0.355
Genotoxicity:  0.59 RPMI-8226 Immunitoxicity:  0.175
A549 Cytotoxicity:  0.511 Hek293 Cytotoxicity:  0.259
BCF:   0.609
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.101
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.275
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.665
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96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota roots n.a. n.a. PMID[16989524]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. rhizome n.a. PMID[22863942]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota aerial parts n.a. n.a. PMID[24042007]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. PMID[38838926]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT34 Cell line BV-2 Mus musculus Inhibition > 80.0 % DrugMatrix in vivo data: Hematology
NPT34 Cell line BV-2 Mus musculus IC50 = 28600.0 nM PMID[18809936]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC471416 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7857 Intermediate Similarity NPC127415
0.7465 Intermediate Similarity NPC34287
0.6438 Remote Similarity NPC94777
0.6203 Remote Similarity NPC8573
0.5875 Remote Similarity NPC44558
0.5802 Remote Similarity NPC282987
0.5488 Remote Similarity NPC112755
0.5488 Remote Similarity NPC170675
0.5443 Remote Similarity NPC183036
0.5385 Remote Similarity NPC78697
0.5301 Remote Similarity NPC210042
0.5301 Remote Similarity NPC77672
0.5301 Remote Similarity NPC133671
0.5301 Remote Similarity NPC135391
0.5301 Remote Similarity NPC78263
0.5301 Remote Similarity NPC250069
0.5238 Remote Similarity NPC145038
0.5238 Remote Similarity NPC56077
0.5238 Remote Similarity NPC281131
0.5238 Remote Similarity NPC253662
0.5238 Remote Similarity NPC179950
0.5238 Remote Similarity NPC88789
0.5238 Remote Similarity NPC491374
0.5122 Remote Similarity NPC474434
0.5119 Remote Similarity NPC19388
0.5119 Remote Similarity NPC240431
0.5119 Remote Similarity NPC55786
0.5119 Remote Similarity NPC95855
0.506 Remote Similarity NPC93099
0.5059 Remote Similarity NPC64305
0.5057 Remote Similarity NPC168584
0.5057 Remote Similarity NPC60735
0.5057 Remote Similarity NPC26230
0.5056 Remote Similarity NPC203050
0.5056 Remote Similarity NPC225434

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC471416 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data